University of Texas SPORE in Lung Cancer: A Collaboration Between The University of Texas Southwestern Medical Center (UTSW) and The University of Texas M. D. Anderson Cancer Center (MDACC). The strategic plan of this SPORE is to identify and understand the molecular "hallmarks of lung cancer" and then translate this information into the clinic for early detection, prevention, prognosis, and the selection and/or development of new treatments for lung cancer. We have invested in several major translational research themes: identification of key lung cancer tumor suppressor genes and their development as novel therapeutics; identification of persons with an increased inherited and/or acquired risk of developing lung cancer by genetic epidemiology and early detection of respiratory epithelial genetic and epigenetic alterations; identification of abnormalities in apoptosis and invasion during lung cancer pathogenesis; understanding signaling pathways that are likely new targets for chemoprevention and therapy of lung cancer; and developing lung cancer therapies directed against telomerase. To achieve these goals, our SPORE has assembled clinicians and basic scientists including medical oncologists, thoracic surgeons, pulmonary physicians, pathologists, molecular geneticists, molecular and cell biologists, epidemiologists, behavioral and psycho-pharmacologists, biostatisticians, and experts in development of new technologies and informatics. The SPORE, brings together two major complementary strengths in lung cancer research involving UTSW and MDACC. This SPORE consists of 5 inter-related projects and 4 supporting Cores. The projects involve: 1. Translation of tumor suppressor genes into new therapeutics for lung cancer; 2. Molecular epidemiology of lung cancer: comparison of surrogate and target tissues markers; 3. Molecular pathology of lung cancer related to apoptosis and invasion and its translation into the clinic; 4.The PI3K pathway as a target for lung cancer prevention and therapy; and 5. Targeting telomerase for lung cancer therapeutics The Cores are: Administrative; Pathology & Tissue Resources; Biostatistics; and Computational Biology & Innovative Technology. All of the scientific projects are: translational in nature; focus on human lung cancer; involve clinical and basic investigators and biostatisticians; interact with the other projects; and utilize Core resources. Innovative Developmental and Career Development Projects have brought new investigators into and stimulated the SPORE that are represented in each of the major projects. We also have a developmental project dealing with new methods of smoking cessation by elucidating genetic contributions to nicotine addiction and response to pharmacological treatment of nicotine addiction. This SPORE also participates in the inter-SPORE effort of the Lung Cancer Biomarkers and Chemoprevention Consortium (LCBCC). Achievement of the aims and objectives of this proposal will result in a major decrease in the incidence, morbidity and mortality of lung cancer.